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Noami Daems,1 Sébastien Penninckx,2 Inge Nelissen,3 Karen Van Hoecke,4 Thomas Cardinaels,4,5 Sarah Baatout,1 Carine Michiels,6 Stéphane Lucas,2 An Aerts11Radiobiology Research Unit, Interdisciplinary Biosciences, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre (SCK.CEN), Mol, Belgium; 2Research Center for the Physics of Matter and Radiation-NARILIS, University of Namur, Namur, Belgium; 3Health Department, Flemish Institute For Technological Research (VITO), Mol, Belgium; 4Radiochemistry Expert Group, Institute for Nuclear Materials Science, Belgian Nuclear Research Centre (SCK.CEN), Mol, Belgium; 5Department of Chemistry, KU Leuven, Heverlee, Belgium; 6Unité de Recherche en Biologie Cellulaire-NARILIS, University of Namur, Namur, BelgiumPurpose: This study evaluates the cytotoxicity of AuNPs coated with polyallylamine (AuNPs-PAA) and conjugated or not to the epidermal growth factor receptor (EGFR)-targeting antibody Cetuximab (AuNPs-PAA-Ctxb) in normal human kidney (HK-2), liver (THLE-2) and microvascular endothelial (TIME) cells, and compares it with two cancer cell lines that are EGFR-overexpressing (A431) or EGFR-negative (MDA-MB-453).Results: Conjugation of Cetuximab to AuNPs-PAA increased the AuNPs-PAA-Ctxb interactions with cells, but reduced their cytotoxicity. TIME cells exhibited the strongest reduction in viability after exposure to AuNPs-PAA(±Ctxb), followed by THLE-2, MDA-MB-453, HK-2 and A431 cells. This cell type-dependent sensitivity was strongly correlated to the inhibition of thioredoxin reductase (TrxR) and glutathione reductase (GR), and to the depolarization of the mitochondrial membrane potential. Both are suggested to initiate apoptosis, which was indeed detected in a concentration- and time-dependent manner. The role of oxidative stress in AuNPs-PAA(±Ctxb)-induced cytotoxicity was demonstrated by co-incubation of the cells with N-acetyl L-cysteine (NAC), which significantly decreased apoptosis and mitochondrial membrane depolarization.Conclusion: This study helps to identify the cells and tissues that could be sensitive to AuNPs and deepens the understanding of the risks associated with the use of AuNPs in vivo.Keywords: cytotoxicity, EGFR, Cetuximab, oxidative stress

Silica nanoparticles (NPs) belong to the industrially most important NP types. In a previous study it was shown that amorphous SiO(2) NPs of 12.5 and 27.0 nm are stable in algal growth inhibition assays and that their ecotoxic effects are related to NP surface area. Here, it was hypothesized and demonstrated that an alumina coating completely alters the particle-particle, particle-test medium and particle-algae interactions of SiO(2) NPs. Therefore, stability and surface characteristics, dissolution, nutrient adsorption and effects on algal growth rate of both alumina coated SiO(2) NPs and bare SiO(2) NPs in OECD algal test medium as a function of pH (6.0-8.6) and natural organic matter (NOM) contents (0-12 mg C/l) were investigated. Alumina coated SiO(2) NPs aggregated in all media and adsorbed phosphate depending on pH and NOM concentration. On the other hand, no aggregation or nutrient adsorption was observed for the bare SiO(2) NPs. Due to their positive surface charge, alumina coated SiO(2) NPs agglomerated with Pseudokirchneriella subcapitata. Consequently, algal cell density measurements based on cell counts were unreliable and hence fluorescent detection of extracted chlorophyll was the preferred method. Alumina coated SiO(2) NPs showed lower toxicity than bare SiO(2) NPs at concentrations ≥46 mg/l, except at pH 6.0. At low concentrations, no clear pH effect was observed for alumina coated SiO(2) NPs, while at higher concentrations phosphate deficiency could have contributed to the higher toxicity of those particles at pH 6.0-6.8 compared to higher pH values. Bare SiO(2) NPs were not toxic at pH 6.0 up to 220 mg/l. Addition of NOM decreased toxicity of both particles. For SiO(2) NPs the 48 h 20% effect concentration of 21.8 mg/l increased 2.6-21 fold and a linear relationship was observed between NOM concentration and effective concentrations. No effect was observed for alumina coated SiO(2) NPs in presence of NOM up to 1000 mg/l. All experiments point out that the alumina coating completely altered NP interactions. Due to the difference in surface composition the SiO(2) NPs, which had the smallest surface area, were more toxic to the alga than the alumina coated SiO(2) NPs. Hence, surface modification can dominate the effect of surface area on toxicity., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The influence of pH (6.0-9.0), natural organic matter (NOM) (0-10 mg C/L) and ionic strength (IS) (1.7-40 mM) on 14 nm CeO₂ NP aggregation and ecotoxicity towards the alga Pseudokirchneriella subcapitata was assessed following a central composite design. Mean NP aggregate sizes ranged between 200 and 10000 nm. Increasing pH and IS enhanced aggregation, while increasing NOM decreased mean aggregate sizes. The 48 h-E(r)C20s ranged between 4.7 and 395.8 mg CeO₂/L. An equation for predicting the 48 h-E(r)C20 (48 h-E(r)C20 = -1626.4 × (pH) + 109.45 × (pH)² + 116.49 × ([NOM]) - 14.317 × (pH) × ([NOM]) + 6007.2) was developed. In a validation study with natural waters the predicted 48 h-E(r)C20 was a factor 1.08-2.57 lower compared to the experimental values., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

The ecological risk assessment of chemicals including nanoparticles is based on the determination of adverse effects on organisms and on the environmental concentrations to which biota are exposed. The aim of this work was to better understand the behavior of nanoparticles in the environment, with the ultimate goal of predicting future exposure concentrations in water. We measured the concentrations and particle size distributions of CeO(2) nanoparticles in algae growth medium and deionized water in the presence of various concentrations and two types of natural organic matter (NOM). The presence of natural organic matter stabilizes the CeO(2) nanoparticles in suspension. In presence of NOM, up to 88% of the initially added CeO(2) nanoparticles remained suspended in deionized water and 41% in algae growth medium after 12d of settling. The adsorbed organic matter decreases the zeta potential from about -15 mV to -55 mV. This reduces aggregation by increased electrostatic repulsion. The particle diameter, pH, electric conductivity and NOM content shows significant correlation with the fraction of CeO(2) nanoparticles remaining in suspension., (Copyright © 2010 Elsevier Ltd. All rights reserved.)